Substance P and its receptors are involved in the effect of histamine H3 receptor agonist, IMETIT on nasal allergic symptoms in guinea pigs
10.3760/cma.j.issn.1673-0860.2010.06.006
- VernacularTitle:组胺H3受体激动剂IMETIT对变应性鼻炎豚鼠P物质及其受体mRNA表达的影响
- Author:
Guang-Ming SUN
1
;
Xu-Dong YANG
;
Xue-Gu XU
;
Pei-Hua LI
;
Wen LIU
;
Li-Juan PAN
Author Information
1. 徐州医学院附属医院
- Keywords:
Histamine agonists;
Rhinitis,allergic;
Imidazoles;
Thiourea;
Substance P;
Receptors,neurokinin-1
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2010;45(6):465-470
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R)mRNA in AR model in guinea pigs. Methods Guinea pigs were divided randomly into 4 groups: AR group (group A) , IMETIT group (group B), Loratadine group (group C) and IMETIT + Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13. 0 software. Results In Group B, the mean (i ± s) number of sneeze [ (15. 0 ± 1. 3) times] , scratching nose [ ( 16. 5 ± 2. 3 ) times ] and respiratory frequency [ (76. 3 ± 4. 1 ) times/min ] were significantly improved than those in group A [ (23. 5 ±2. 6) times, (26. 1 ±4. 1) times and (66. 5 ±5. 8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP positive cells [(11. 6 ±3. 6)/HP] and SP-R mRNA expression (0.64 ±0.04 ) in group B were reduced significantly compared to group A [ (27. 1 ± 9. 7)/HP, (0. 83 ± 0. 03 ) , P value were 0. 000, 0. 000, respectively]. Sneeze [(10.0 ±2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [ (90. 0 ±5. 0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0. 002 and 0. 000, respectively). SP-positive cells [ (2. 0 ± 1. 7)/HP] and SP-R mRNA expression (0. 52 ±0. 06) in Group D compared with group B were also significantly reduced (P value were 0. 012 and 0. 000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11. 59, 8. 28,5. 61,5.48,6. 50, respectively, P value were 0. 002, 0. 008, 0. 025, 0. 027, 0. 017). Conclusions IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-RmRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.
